Therapeutic investigation of the factors leading to the molecular abnormalities in heart failure
| Project/Area Number |
16590662
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAO Atsushi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70372381)
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| Co-Investigator(Kenkyū-buntansha) |
KINUGAWA Koichiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (00345216)
碓井 伸一 東京大学, 医学部附属病院, 医員
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | heart failure / hypertrophy / pulmonary arterial hypertension / monocrotaline / fetal gene / angiotensin II / valsartan / carvedilol / 筋小胞体 / 心肥大 / BNP / 胎児型遺伝子 |
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| Research Abstract |
Background
Left ventricular remodeling might be involved in the pathophysiology of right ventricular hypertrophy/failure due to pulmonary arterial hypertension (PAH), while left ventricle is considered not under pressure/volume overload.
Methods and Results
We used rats with monocrotaline (MCT) -induced PAH to examine whether up-regulated neurohumoral factors may induce left ventricular remodeling and(/or) contribute to prognosis. Morphological analysis revealed a significant increase in the weight of the free walls of both ventricles and the inter-ventricular septum in MCT rats, indicating biventricular hypertrophy, while the systemic blood pressure was not elevated. RNase protection assay demonstrated the activation of fetal gene program in cardiac muscle of the left and right ventricular free walls in MCT rats. The similar activation of the fetal gene program was observed in the left ventricle of rats continuously infused with angiotensin (AT) II, while this was not the case for rats infused with isoproterenol. Measured plasma levels of AT II, noradrenaline, and brain natriuretic peptide (BNP) were all significantly elevated in MCT rats. Furthermore, the plasma BNP level was positively correlated with the ratio of heart weight to body weight and the plasma level of AT II in MCT rats. Not right but left ventricular hypertrophy was significantly reduced by the treatment with an AT II type 1 receptor blocker, valsartan in MCT rats, while the effect of an adrenergic α_1 and (β_<1,2> blocker, carvedilol, was border. Survival rate in MCT rats was significantly improved when MCT rats were treated with valsartan or carvedilol.
Conclusions
Up-regulated neurohumoral factors seem to play an important role in left ventricular remodeling as well as right ventricular hypertrophy/failure, and are associated with impairment of prognosis in PAH rats.
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Report
(3 results)
Research Products
(4 results)
